Crystal-induced neutrophil activation VI. Involvment of FcgammaRIIIB (CD16) and CD11b in response to inflammatory microcrystals.
The inflammatory reaction associated with the deposition of monosodium urate (MSU) crystals in synovial spaces is known to be due to interactions with polymorphonuclear neutrophils mediated by presently unidentified surface structures. In this study, we have observed that antibodies directed against CD16 (VIFcRIII) and CD11b (VIM12) selectively and potently inhibit the activation of neutrophils by MSU crystals. The responses affected include the stimulation of tyrosine phosphorylation, activation of the tyrosine kinase syk, tyrosine phosphorylation of the proto-oncogene Cbl, mobilization of calcium, and stimulation of the activity of phospholipase D and of the production of superoxide anions. Tyrosine phosphorylation responses to MSU crystals develop during the Me2SO4-induced differentiation of HL-60 cells in parallel with the surface expression of CD16. These data strongly support the hypothesis that inflammatory microcrystals interact opportunistically with CD16 initially, and that the signal transduction pathways activated thereby depend on CD11b. An examination of the relevance of the hypothesis that an uncontrolled activation of CD16/CD11b may play a role in inflammatory reactions associated with a dysregulation of neutrophil function (other than crystal arthropathies) appears warranted on the basis of the present results.
Barabé
F
F
Centre de Recherche en Rhumatologie et Immunologie, Department of Medicine, Faculty of Medicine, Laval University, Ste-Foy, Québec, Canada.
Gilbert
C
C
Liao
N
N
Bourgoin
S G
SG
Naccache
P H
PH
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology; D002118:Calcium / Q000097:blood; D003460:Crystallization; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D017452:Receptors, IgG / Q000502:physiology*; D013481:Superoxides / Q000097:blood; D014527:Uric Acid / Q000737:chemistry / Q000494:pharmacology*
D000906:Antibodies; D015703:Antigens, CD; C000715470:MAS1 protein, human; D016177:Macrophage-1 Antigen; D000090063:Proto-Oncogene Mas; D017452:Receptors, IgG; D013481:Superoxides; D019000:Phosphotyrosine; D014527:Uric Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium